Mortality trends in idiopathic pulmonary fibrosis in Europe between 2013 and 2018.

INTRODUCTION: Previous research has suggested that the incidence of idiopathic pulmonary fibrosis (IPF) is increasing in the United Kingdom (UK) and elsewhere. The aim of this study is to provide contemporary estimates of IPF mortality rates across 24 European Countries from 2013 to 2018, using death certificates data from the European Statistics Institution (EUROSTAT) database. METHODS: We extracted country data for IPF (International Classification of Diseases 10th Edition, ICD-10, code "J84.1") mortality from the EUROSTAT dataset. We calculated country- age- and sex-specific death registration rates between 2013 and 2018. We used direct standardisation to compare rates between countries. We calculated annual trends in mortality rate ratios using a segmented regression model. RESULTS: The overall standardised mortality rate in EU Countries during this period was 3.90 per 10 0000 person-years (95%, CI 3.80-3.90), with the rate raising from 3.70 in the 2013 to 4.00 in the 2018 (average annual percent change: 1.74%, 95% CI 0.91-2.59). We observed substantial inter-country differences, with the highest rates detected in Ireland, the UK, and Finland, the lowest rate in Bulgaria, and middle rates in Germany, Greece, Italy, the Netherlands, Portugal, and Slovenia. CONCLUSION: In summary, the IPF mortality rate is increasing across Europe. There are currently more than 17 000 deaths recorded from IPF each year in Europe but the marked geographical differences we observed suggest that this figure may underestimate the true rate considerably.

PCSK6 and Survival in Idiopathic Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. A better understanding of the molecular drivers of IPF progression is needed. Objectives: To identify and validate molecular determinants of IPF survival. Methods: A staged genome-wide association study was performed using paired genomic and survival data. Stage I cases were drawn from centers across the United States and Europe and stage II cases from Vanderbilt University. Cox proportional hazards regression was used to identify gene variants associated with differential transplantation-free survival (TFS). Stage I variants with nominal significance (P < 5 × 10-5) were advanced for stage II testing and meta-analyzed to identify those reaching genome-wide significance (P < 5 × 10-8). Downstream analyses were performed for genes and proteins associated with variants reaching genome-wide significance. Measurements and Main Results: After quality controls, 1,481 stage I cases and 397 stage II cases were included in the analysis. After filtering, 9,075,629 variants were tested in stage I, with 158 meeting advancement criteria. Four variants associated with TFS with consistent effect direction were identified in stage II, including one in an intron of PCSK6 (proprotein convertase subtilisin/kexin type 6) reaching genome-wide significance (hazard ratio, 4.11 [95% confidence interval, 2.54-6.67]; P = 9.45 × 10-9). PCSK6 protein was highly expressed in IPF lung parenchyma. PCSK6 lung staining intensity, peripheral blood gene expression, and plasma concentration were associated with reduced TFS. Conclusions: We identified four novel variants associated with IPF survival, including one in PCSK6 that reached genome-wide significance. Downstream analyses suggested that PCSK6 protein plays a potentially important role in IPF progression.

Brain drain in pediatric anesthesiology: The geographic and demographic distribution of national origin among pediatric anesthesiologists in the United States.

BACKGROUND: American pediatric anesthesiologists have a long history of international volunteerism. However, the US healthcare system also benefits from the contributions of a large number of physicians who come from other nations to work within its borders. Despite this fact, little is known about the contribution of international medical graduates (IMG) to the pediatric anesthesiology subspecialty. AIMS: To characterize the contribution of IMG to the field of pediatric anesthesiology in the United States, and to elucidate the geographic and demographic distribution of their national origins so as to understand the movement of skilled personnel between countries. METHODS: Online physician directories of American children's hospitals were searched, and anesthesiologists were recorded for their national origin of medical education. International graduates were reported as a percentage of the pediatric anesthesiology workforce. Those attending medical colleges catering to American students ("offshore" medical schools) were analyzed separately from other IMGs. The cohort of non-offshore IMGs were analyzed for national and continental origins, and by national level of economic development. RESULTS: Of 1979 anesthesiologists analyzed, 397 attended medical school outside the United States, with 58 being from offshore schools. The remaining 338 represented 17.1% of the total pediatric anesthesiology workforce. They came from 58 countries on six continents. Of those, 65.1% attended medical school in low- and middle-income countries. CONCLUSIONS: International medical graduates, disproportionately from low- and middle-income countries, compose a large proportion of the US Pediatric Anesthesiology workforce. While these clinicians play a vital role in providing care for American children, the potential impacts of skilled physician loss on their nations of origin must also be considered.

Impact of the SARS-CoV-2 pandemic on lung cancer survival in England: an analysis of the rapid cancer registration dataset.

Early changes in lung cancer care can affect survival. Given the decrease in diagnosis during lockdowns, we calculated their impact on survival using National Lung Cancer Audit data. Percentage survival and HRs for death were compared between 2019 and lockdown periods of 2020. Decreased survival was observed from the first national lockdown onwards and within 90 days of diagnosis. HRs were highest for people diagnosed at the end of 2020 at 1.26 (95% CI 1.20 to 1.32) for death within 90 days and 1.51 (95% CI 1.42 to 1.60) for death between 91 and 270 days. Further work is needed on measures to mitigate this impact.

COVID-19 infection, admission and death and the impact of corticosteroids among people with rare autoimmune rheumatic disease during the second wave of COVID-19 in England: results from the RECORDER Project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the second wave of the COVID-19 pandemic in England, and describe the impact of corticosteroids on outcomes. METHODS: Hospital Episode Statistics data were used to identify people alive on 1 August 2020 with ICD-10 codes for RAIRD from the whole population of England. Linked national health records were used to calculate rates and rate ratios of COVID-19 infection and death up to 30 April 2021. Primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. NHS Digital and Office for National Statistics general population data were used for comparison. The association between 30-day corticosteroid usage and COVID-19-related death, COVID-19-related hospital admissions and all-cause deaths was also described. RESULTS: Of 168 330 people with RAIRD, 9961 (5.92%) had a positive COVID-19 PCR test. The age-standardized infection rate ratio between RAIRD and the general population was 0.99 (95% CI: 0.97, 1.00). 1342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.76 (95% CI: 2.63, 2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes. CONCLUSIONS: During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared with the general population, with corticosteroids associated with increased risk.

Ninety-day mortality following lung cancer surgery: outcomes from the English national clinical outcomes audit.

Accurately explaining perioperative mortality and risk to patients is an essential part of shared decision making. In the case of lung cancer surgery, the currently available multivariable mortality prediction tools perform poorly, and could mislead patients. Using data from 2004 to 2012, this group has previously produced data tables for 90-day postoperative mortality, to be used as a communication aid in the consenting process. Using National Lung Cancer Clinical Outcomes audit data from 2017 to 2018, we have produced updated early mortality tables, to reflect current thoracic surgery practice.

Selection of eligible participants for screening for lung cancer using primary care data.

Lung cancer screening is effective if offered to people at increased risk of the disease. Currently, direct contact with potential participants is required for evaluating risk. A way to reduce the number of ineligible people contacted might be to apply risk-prediction models directly to digital primary care data, but model performance in this setting is unknown. METHOD: The Clinical Practice Research Datalink, a computerised, longitudinal primary care database, was used to evaluate the Liverpool Lung Project V.2 (LLPv2) and Prostate Lung Colorectal and Ovarian (modified 2012) (PLCOm2012) models. Lung cancer occurrence over 5-6 years was measured in ever-smokers aged 50-80 years and compared with 5-year (LLPv2) and 6-year (PLCOm2012) predicted risk. RESULTS: Over 5 and 6 years, 7123 and 7876 lung cancers occurred, respectively, from a cohort of 842 109 ever-smokers. After recalibration, LLPV2 produced a c-statistic of 0.700 (0.694-0.710), but mean predicted risk was over-estimated (predicted: 4.61%, actual: 0.9%). PLCOm2012 showed similar performance (c-statistic: 0.679 (0.673-0.685), predicted risk: 3.76%. Applying risk-thresholds of 1% (LLPv2) and 0.15% (PLCOm2012), would avoid contacting 42.7% and 27.4% of ever-smokers who did not develop lung cancer for screening eligibility assessment, at the cost of missing 15.6% and 11.4% of lung cancers. CONCLUSION: Risk-prediction models showed only moderate discrimination when applied to routinely collected primary care data, which may be explained by quality and completeness of data. However, they may substantially reduce the number of people for initial evaluation of screening eligibility, at the cost of missing some lung cancers. Further work is needed to establish whether newer models have improved performance in primary care data.

Biomarker signatures for progressive idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers have the potential for guiding management in clinical practice. We assessed the prognostic role of serum biomarkers in three independent IPF cohorts: Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE). METHODS: In the AIPFR cohort, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. LASSO (least absolute shrinkage and selection operator) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at 1 year in the AIPFR cohort, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in the PROFILE cohort. Four significantly replicating biomarkers were aggregated into a progression index model based on tertiles of circulating concentrations. RESULTS: 189 participants were included in the AIPFR cohort, 205 participants from the TLF cohort and 122 participants from the PROFILE cohort. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at 1 year. Proteomic data did not replicate. The progression index in the AIPFR, TLF and PROFILE cohorts predicted risk of progression, mortality and progression-free survival. A statistical model incorporating the progression index demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP (gender, age and physiology) score model alone in all cohorts, and significantly so within the incidence-based TLF and PROFILE cohorts. CONCLUSION: A panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.

COVID-19 infection, admission and death among people with rare autoimmune rheumatic disease in England: results from the RECORDER project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared with the general population. METHODS: We used Hospital Episode Statistics to identify all people alive on 1 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths. RESULTS: We identified a cohort of 168 680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardized infection rate was 1.54 (95% CI: 1.50, 1.59) times higher than in the general population. A total of 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.41 (2.30-2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. CONCLUSIONS: During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared with the general population. These increases were seen despite shielding policies.

Validation of diagnostic coding for interstitial lung diseases in an electronic health record system in Hong Kong.

OBJECTIVE: Large electronic medical record (EMR) databases can facilitate epidemiology research into uncommon diseases such as interstitial lung disease (ILD). Given the rarity and diagnostic difficulty of ILD, the validity of the coding in EMR requires clarification. We aimed to assess the validity of International Classification of Diseases, 9th Revision (ICD-9) code algorithms for identifying ILD in the territory-wide electronic medical health record system of Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. METHOD: Patients who visited the Queen Mary Hospital in 2005-2018 with ILD were identified using the following ICD-9 codes: post-inflammatory pulmonary fibrosis (PPF; ICD-9: 515), idiopathic fibrosing alveolitis (IFA; ICD-9: 516.3), connective tissue disease-associated interstitial lung disease (CTD-ILD; ICD-9: 517.2, 517.8, 714.81), sarcoidosis (ICD-9: 135) and extrinsic allergic alveolitis (EAA; ICD-9: 495). A random selection was conducted in cases with diagnostic code of PPF and IFA, where a relative higher case number was identified. All the cases of CTD-ILD, sarcoidosis and EAA were included in validation for relatively small case number. RESULTS: Two hundred and sixty nine cases were validated using medical record review by a respiratory specialist. The overall positive predictive value (PPV) was 79% (95% CI, 74%-84%). In subgroup analysis, true positive case numbers of PPF, IFA, CTD-ILD, sarcoidosis and EAA were 74/100 (74%), 95/100 (95%), 11/15 (73%), 27/32 (84%) and 6/22 (27%), respectively. CONCLUSIONS: This was the first ICD-9 coding validation for ILD in Hong Kong CDARS. Our study demonstrated that using ICD-9 algorithms 515, 516.3, 517.2, 517.8, 714.81 and 135 enhanced identifications of ILDs with PPV that was reliable to support utility of CDARS database for further clinical research on ILDs. The validity is particularly high with 516.3.

Using patient experiences to evaluate care and expectations in lung cancer: analysis of the English Cancer Patient Experience Survey linked with the national cancer registry.

PURPOSE: Identification of unmet needs in person centred and supportive care could be limited by differences in experience across specific cancer populations. Using the experiences of people with lung cancer, we assess distinctions according to demographic and clinical characteristics. METHODS: The English Cancer Patient Experience Survey was linked to the national cancer registry. The primary outcome was experience of the lung cancer pathway when assessed in multi-question models developed with item response theory. Secondary outcomes were experience by treatment received and in separate dimensions of the care pathway: up to diagnosis, treatment information, and staff support. RESULTS: Responses from 15,967 adults with a lung cancer diagnosis between 2009 and 2015 were included. Positive experiences were more likely to be reported by people aged between 65 and 80 (adjusted coefficient 0.08, 95%CI 0.05;0.11), those living in the most deprived areas (adjusted coefficient 0.10, 95%CI 0.05;0.14), diagnosed at lung cancer stage IIA-B (adjusted coefficient 0.09, 95%CI 0.04;0.14), and those diagnosed through inpatient elective admissions (adjusted coefficient 0.17, 95%CI 0.07;0.28). Specific experiences differed across dimensions of care and within lung cancer treatment groups. CONCLUSIONS: Experiences differed according to gender and ethnicity, supporting previous observations in cancer. In contrast to previous studies, people with lung cancer were more likely to report positive pathway experiences at older ages, living in more deprived areas, or diagnosed after stage I, all frequently associated with worse clinical outcomes. The distinct observations in lung cancer specific analyses suggest potential unmet needs, such as in early stage disease and younger age groups.

Intraarterial papaverine for relief of catheter-induced peripheral arterial vasospasm during pediatric cardiac surgery: A randomized double-blind controlled trial.

BACKGROUND: Maintaining the patency of peripheral arterial lines in pediatric patients during surgery can be challenging due to multiple factors, and catheter-related arterial vasospasm is a potentially modifiable cause. Papaverine, a potent vasodilator, improves arterial line patency when used as a continuous infusion in the pediatric intensive care setting, but this method is not convenient during surgery. AIM: Extrapolating from the benefit seen in the intensive care unit, the authors hypothesize that a small-volume intraarterial bolus of papaverine immediately after arterial line placement will reduce vasospasm-related arterial line malfunction. METHODS: This was a prospective, randomized, double-blind study. Patients less than 17 years of age undergoing cardiac surgery were enrolled. Patients were randomized into the heparin or papaverine groups. Immediately after arterial line insertion, an intraarterial bolus of heparin (2 units/ml, 1 ml) or papaverine (0.12 mg/ml, 1 ml) was administered (T1, Figure 1). An optimal waveform was defined as the ease of aspirating a standardized blood sample within 30 s, absence of cavitation when sampling, absence of color change at the catheter site during injection, and presence of a dicrotic notch. The primary outcome evaluated was the presence of an optimal arterial waveform at 5 min after the first randomized dose (T1 + 5 min). The secondary outcomes were the presence of optimal arterial waveform an hour after the first dose and the ability of papaverine to rescue suboptimal waveforms. RESULTS: A total of 100 patients were enrolled in the study. Twelve patients were excluded from the analysis. Complete datasets after randomization were available in 88 patients (heparin group, n = 46; papaverine group, n = 42). At baseline, groups were similar for age, weight, arterial vessel size, and arterial line patency. At T1 + 5 min, an improvement in the waveform characteristics was observed in the papaverine group (heparin,39% [8/46] vs. papaverine, 64% [27/42]; p = .02; odds ratio, 2.8; 95% CI, 1.2 to 6.6, Figure 3, Table 2). At the end of 1 h, both groups showed continued improvement in arterial line patency. After the second dose, a higher number of patients in the heparin group had suboptimal waveforms and were treated with papaverine (heparin,37% [17/46] vs. papaverine,17% [7/42], p = .05). Patients in the heparin group treated with papaverine showed significant improvement in patency (13/17 vs. 3/7, p = .01). No serious adverse events were reported. CONCLUSIONS: In pediatric patients, papaverine injection immediately after peripheral arterial catheter placement was associated with relief of vasospasm and improved initial arterial line patency. Further, papaverine can be used as a rescue to improve and maintain arterial line patency.

An intelligent early warning system of analyzing Twitter data using machine learning on COVID-19 surveillance in the US.

The World Health Organization (WHO) declared on 11th March 2020 the spread of the coronavirus disease 2019 (COVID-19) a pandemic. The traditional infectious disease surveillance had failed to alert public health authorities to intervene in time and mitigate and control the COVID-19 before it became a pandemic. Compared with traditional public health surveillance, harnessing the rich data from social media, including Twitter, has been considered a useful tool and can overcome the limitations of the traditional surveillance system. This paper proposes an intelligent COVID-19 early warning system using Twitter data with novel machine learning methods. We use the natural language processing (NLP) pre-training technique, i.e., fine-tuning BERT as a Twitter classification method. Moreover, we implement a COVID-19 forecasting model through a Twitter-based linear regression model to detect early signs of the COVID-19 outbreak. Furthermore, we develop an expert system, an early warning web application based on the proposed methods. The experimental results suggest that it is feasible to use Twitter data to provide COVID-19 surveillance and prediction in the US to support health departments' decision-making.

Risk of death among people with rare autoimmune diseases compared with the general population in England during the 2020 COVID-19 pandemic.

OBJECTIVES: To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared with the general population, and compared with their pre-COVID risk. METHODS: We conducted a cohort study in Hospital Episode Statistics for England from 2003 onwards, and linked data from the NHS Personal Demographics Service. We used ONS published data for general population mortality rates. RESULTS: We included 168 691 people with a recorded diagnosis of RAIRD alive on 1 March 2020. Their median age was 61.7 (IQR 41.5-75.4) years, and 118 379 (70.2%) were female. Our case ascertainment methods had a positive predictive value of 85%. A total of 1815 (1.1%) participants died during March and April 2020. The age-standardized mortality rate (ASMR) among people with RAIRD (3669.3; 95% CI: 3500.4, 3838.1 per 100 000 person-years) was 1.44 (95% CI: 1.42, 1.45) times higher than the average ASMR during the same months of the previous 5 years, whereas in the general population of England it was 1.38 times higher. Age-specific mortality rates in people with RAIRD compared with the pre-COVID rates were higher from the age of 35 upwards, whereas in the general population the increased risk began from age 55 upwards. Women had a greater increase in mortality rates during COVID-19 compared with men. CONCLUSION: The risk of all-cause death is more prominently raised during COVID-19 among people with RAIRD than among the general population. We urgently need to quantify how much risk is due to COVID-19 infection and how much is due to disruption to health-care services.

Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterized by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of association implicating multiple pathways including host defense, telomere maintenance, signaling, and cell-cell adhesion.Objectives: To improve our understanding of factors that increase IPF susceptibility by identifying previously unreported genetic associations.Methods: We conducted genome-wide analyses across three independent studies and meta-analyzed these results to generate the largest genome-wide association study of IPF to date (2,668 IPF cases and 8,591 controls). We performed replication in two independent studies (1,456 IPF cases and 11,874 controls) and functional analyses (including statistical fine-mapping, investigations into gene expression, and testing for enrichment of IPF susceptibility signals in regulatory regions) to determine putatively causal genes. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF.Measurements and Main Results: We identified and replicated three new genome-wide significant (P < 5 × 10-8) signals of association with IPF susceptibility (associated with altered gene expression of KIF15, MAD1L1, and DEPTOR) and confirmed associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as yet unreported IPF susceptibility variants contribute to IPF susceptibility.Conclusions: The observation that decreased DEPTOR expression associates with increased susceptibility to IPF supports recent studies demonstrating the importance of mTOR signaling in lung fibrosis. New signals of association implicating KIF15 and MAD1L1 suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility.

Incidence and predictors of idiopathic pulmonary fibrosis complicating Type 2 diabetes: the Fremantle Diabetes Study Phase I.

During 106 865 person-years of follow up, 17 (1.3%) Fremantle Diabetes Study Phase I participants with Type 2 diabetes and 57 (1.1%) matched individuals without diabetes developed idiopathic pulmonary fibrosis (IPF), an incidence rate ratio (95% confidence interval) of 1.40 (0.76-2.44) (P = 0.22). In the diabetes cohort, age at diabetes diagnosis and total serum cholesterol (inversely) predicted incident IPF in competing risk multivariable models. The incidence of IPF was low in community-based cohorts, regardless of Type 2 diabetes status.

Post-treatment survival difference between lobectomy and stereotactic ablative radiotherapy in stage I non-small cell lung cancer in England.

BACKGROUND: Approximately 15%-20% of all non-small cell lung cancer (NSCLC) cases present with stage I disease. Surgical resection traditionally offers the best chance of a cure but some patients will not have this treatment due to older age, comorbidities or personal choice. Stereotactic ablative radiotherapy (SABR) has become an established curative intent treatment option for patients who are not selected for or do not choose surgery. The aim of this study is to compare survival at 90 days, 6 months, 1 year and 2 years for patients who received either lobectomy or SABR. METHODS: We used data from the 2015 National Lung Cancer Audit database and linked with Hospital Episode Statistics and the radiotherapy dataset to identify patients with NSCLC stage IA-IB and performance status (PS) 0-2 who underwent surgery or SABR treatment. We assessed the likelihood of death at 90 days, 6 months, 1 year and 2 year after diagnosis and procedure date to observe survival between two patient groups. RESULTS: We identified 2373 patients in our cohort, 476 of whom had SABR. The median difference between date of diagnosis and date of treatment for surgery patients was 17 days while for SABR patients it was 73 days. Increasing age and worsening PS were associated with having SABR rather than surgery. Survival between the two treatment modalities was similar early on but by 1-year people who had surgery did better than those who had SABR (adjusted ORs 2.12, 95% CI 1.35 to 2.31). This difference persisted at 2 years and when the analysis was restricted to patients aged <80 years and with PS 0 or 1 and stage IA only. CONCLUSION: Our analysis suggests that patients who have lobectomy have a better survival compared with SABR patients; however, we found considerable delays in patients receiving SABR which may contribute to poorer long-term outcomes with this treatment option. Reducing these delays should be a key focus in development and reorganisation of services.

Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis.

Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10-27) and subpleural ILAs (P = 1.6 × 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10-8) and FCF1P3 (rs73199442, P = 4.8 × 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10-8) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P < 0.05/12) with ILAs.Conclusions: In a GWAS of ILAs in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.

Anesthetic management of catheter-based patent ductus arteriosus closure in neonates weighing <3 kg: A Retrospective Observational Study.

BACKGROUND: The patent ductus arteriosus is a cardiac lesion commonly found in premature neonates. Though surgical closure via thoracotomy is the most definitive treatment option, it is associated with significant morbidity. New catheter-based closure options offer a potentially safer alternative treatment, even in premature neonates. However, no literature reports the anesthetic techniques, challenges, and risks associated with this procedure in this population. AIM: This study documents the anesthetic challenges and potential complications associated with the management of catheter-based closure of the ductus arteriosus in neonates under 3 kg. METHODS: This single-center, retrospective study examined patients who underwent catheter-based ductus arteriosus closure between August 2015 and February 2019. A clinical protocol for anesthetic management of these patients was utilized throughout the study period. Clinical outcomes considered were new hemodynamic instability or vasoactive medication requirements, hypothermia, prolonged intubation (>3 days postoperatively), postprocedure acute kidney injury, perioperative red blood cell transfusion, and accidental extubation. RESULTS: Seventy-six neonates underwent 78 procedures. No patient developed perioperative hemodynamic instability, vasoactive medication requirements, or acute kidney injury. Four patients (5%) required red blood cell transfusion, two (3%) became hypothermic, and one (1%) was accidentally extubated. Closure was achieved in 73 patients (96%) on the first attempt. However, 17 patients (40%) required prolonged periods of mechanical ventilation following the procedure. CONCLUSION: Despite multiple clinical and logistical challenges, anesthetic risk associated with catheter-based PDA closure in small neonates can be effectively managed through standardized and multidisciplinary care.

Surveillance of Noncommunicable Disease Epidemic Through the Integrated Noncommunicable Disease Collaborative Management System: Feasibility Pilot Study Conducted in the City of Ningbo, China.

BACKGROUND: Noncommunicable diseases (NCDs) have become the main public health concern worldwide. With rapid economic development and changes in lifestyles, the burden of NCDs in China is increasing dramatically every year. Monitoring is a critical measure for NCDs control and prevention. However, because of the lack of regional representativeness, unsatisfactory data quality, and inefficient data sharing and utilization, the existing surveillance systems and surveys in China cannot track the status and transition of NCDs epidemic. OBJECTIVE: To efficaciously track NCDs epidemic in China, this pilot program conducted in Ningbo city by the Chinese Center for Disease Control and Prevention (CDC) aimed to develop an innovative model for NCDs surveillance and management: the integrated noncommunicable disease collaborative management system (NCDCMS). METHODS: This Ningbo model was designed and developed through a 3-level (county/district, municipal, and provincial levels) direct reporting system based on the regional health information platform. The uniform data standards and interface specifications were established to connect different platforms and conduct data exchanges. The performance of the system was evaluated based on the 9 attributes of surveillance system evaluation framework recommended by the US CDC. RESULTS: NCDCMS allows automatic NCDs data exchanging and sharing via a 3-level public health data exchange platform in China. It currently covers 201 medical institutions throughout the city. Compared with previous systems, automatic popping up of the report card, automatic patient information extraction, and real-time data exchange process have highly improved the simplicity and timeliness of the system. The data quality meets the requirements to monitor the incidence trend of NCDs accurately, and the comprehensive data types obtained from the database (ie, directly from the 3-level platform on the data warehouse) also provide a useful information to conduct scientific studies. So far, 98.1% (201/205) of medical institutions across Ningbo having been involved in data exchanges with the model. Evaluations of the system performance showed that NCDCMS has high levels of simplicity, data quality, acceptability, representativeness, and timeliness. CONCLUSIONS: NCDCMS completely reshaped the process of NCD surveillance reporting and had unique advantages, which include reducing the work burden of different stakeholders by data sharing and exchange, eliminating unnecessary redundancies, reducing the amount of underreporting, and structuring population-based cohorts. The Ningbo model will be gradually promoted elsewhere following this success of the pilot project, and is expected to be a milestone in NCDs surveillance, control, and prevention in China.